POS1424 AQUAPORIN EXPRESSION IN LUPUS NEPHRITIS: INSIGHTS INTO TUBULAR PATHOLOGY
Authors: M. Melchior, M. Van Eycken, C. Nicaise, T. Duquesne, L. Longueville, C. Decaestecker, I. Salmon, C. Delporte, M. Soyfoo
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Lupus nephritis is a severe and life-threatening manifestation of systemic lupus erythematosus. Tubulointerstitial hypoxia is a key factor in the progression to end-stage renal disease. Numerous aquaporins are expressed by renal tubules and are essential for their proper functioning. Several mouse models have shown their involvement in the regulation of renal inflammation during acute stress episodes. However, the expression of aquaporins (AQP) in human lupus nephritis has been poorly studied. <h3>Objectives</h3> The aim of this study is to characterise the tubular expression of AQP1, AQP2 and AQP3 which could provide a better understanding of tubulointerstitial stress during lupus nephritis. <h3>Methods</h3> This retrospective monocentric study was conducted at Erasme-HUB Hospital, Brussels with the approval of the ULB-Erasme Ethical Committee (P2020/710). A total of 37 lupus nephritis samples and 9 healthy samples collected between 2000 and 2020 were obtained from the biobank of the pathology department. Kidney biopsy sections were reviewed according to the ISN/RPS 2018 classification. Immunohistochemistry was performed to detect AQP1, AQP2 and AQP3 and followed by digital image analysis. Digital image quantification analysis was performed using ImageJ software. <h3>Results</h3> We observed weak expression of AQP1 in glomeruli and strong expression on the apical side of proximal convoluted tubules in the cortex. In the medulla, it was confined to the descending loop of Henle and the vasa recta. AQP2 was exclusively expressed on the apical side of collecting tubules in both the cortex and the medulla. AQP3 was not detected in glomeruli, weakly expressed on the basolateral side of proximal convoluted tubules, and strongly expressed on the basolateral side of distal convoluted tubules and collecting tubules. No difference in staining location was found between healthy and lupus nephritis kidney biopsies. By digital quantitative analysis, we observed a significant decrease in AQP1 expression in the renal cortex (p&lt;0.0001), a non-significant trend towards a decrease in AQP2 expression and a significant cortical and medullary decrease in AQP3 expression (p&lt;0.001). This decrease was more pronounced in the subgroup of membranoproliferative glomerulonephritis (class III/IV), particularly for AQP3 (p&lt;0.05). Within the subgroup of membranoproliferative glomerulonephritis, there was a strong negative correlation between both cortical and medullary AQP2 expression and interstitial inflammation (r=-0.5238; p&lt;0.01). Decreased cortical AQP3 expression was strongly negatively correlated with interstitial fibrosis (r=-0.6651; p&lt;0.001) and tubular atrophy (r=--0.6651; p&lt;0.001). <h3>Conclusion</h3> We found a significant decrease in the expression of several AQPs in the parenchyma of lupus nephritis. We believe that this decrease is a feature of tubulointerstitial damage. Immunohistochemical analyses of AQPs on lupus nephritis samples could help to assess the tubulointerstitial hypoxia and cell damage and therefore renal prognosis. <h3>References</h3> [1]Maria, N.I., Davidson, A. Protecting the kidney in systemic lupus erythematosus: from diagnosis to therapy. Nat Rev Rheumatol 16, 255–267 (2020). [2]Matsuzaki, T., Yaguchi, T., Shimizu, K. et al. The distribution and function of aquaporins in the kidney: resolved and unresolved questions. Anat Sci Int 92, 187–199 (2017). <h3> Acknowledgements</h3> We thank DIAPath for their technical assistance. The CMMI is supported by the European Regional Development Fund and the Walloon Region. <h3>Disclosure of Interests</h3> None Declared.